Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phenylketonuria is a genetic defect that, without strict dietary control, results in the accumulation of phenylalanine (Phe) in body fluids. If a low-Phe diet is not maintained during pregnancy, the offspring of phenylketonuric women are born with mental retardation and microcephaly. Primary cultures of rat cerebellar granule cells, rat cortical astrocytes, human fetal astrocytes, and human neuroblastoma (SY5Y) cells and human astrocytoma (1321N1) cells were used to test the hypothesis that the microencephaly may be a result of neuronal cell death and reduced astrocyte proliferation. Exposure to Phe or to six Phe metabolites [phenylacetic acid (PAA), phenyllactic acid, hydroxyphenylacetic acid, phenylpyruvic acid, phenylethylamine (PEA), and mandelic acid] did not result in astroglial or neuronal cell cytotoxicity. Treatment of 1321N1 cells, human fetal astrocytes, or rat astrocytes with 5 mM Phe for 24 h decreased DNA synthesis 19 +/- 4, 30 +/- 4, and 60 +/- 6%, respectively. This effect was concentration dependent, and flow cytometry revealed that Phe treatment resulted in the accumulation of cells in the G(0)/G(1) phase of the cell cycle. In addition, in 1321N1 cells, exposure to 5 mM PAA, and in rat astrocytes, exposure to 0.5 mM PEA inhibited cell proliferation 42 +/- 4 and 55 +/- 4%, respectively. These metabolites also resulted in the accumulation of cells in the G(0)/G(1) phase of the cell cycle. In human fetal astrocytes, 0.5 mM PEA and 0.5 mM PAA resulted in a 41 +/- 12 and 52 +/- 11% reduction proliferation, respectively.
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PMID:Effect of phenylalanine and its metabolites on the proliferation and viability of neuronal and astroglial cells: possible relevance in maternal phenylketonuria. 1099 93

The steroid SC17599 (17alpha-acetoxy-6-dimethylaminomethyl-21-fluoro-3-ethoxypregna -3, 5-dien-20-one) has mu-opioid actions in vivo. The ability of SC17599 to interact with opioid receptors has been studied using radioligand and [(35)S]guanosine-5'-O-(3-thio)triphosphate (GTPgammaS) binding assays. SC17599 bound to mu-opioid receptors in SH-SY5Y neuroblastoma cells and to recombinant receptors expressed in rat C6 glioma cells and Chinese hamster ovary cells with good affinity and with greater than 100-fold selectivity for mu- over both delta- and kappa-opioid receptors. Binding was much reduced when aspartate 147 in the wild-type mu-opioid receptor was replaced with asparagine. The affinity of SC17599 for the mu-opioid receptor was decreased in the presence of sodium ions, indicating agonist activity. SC17599 stimulated the binding of [(35)S]GTPgammaS in a naloxone-reversible manner with good potency and maximal effect equivalent to that of the mu-opioid agonists fentanyl and [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin. In rat brain membranes, SC17599-mediated stimulation of [(35)S]GTPgammaS binding was reversed by the antagonist naltrexone. SC17599 lacks an aromatic ring and para-hydroxyl substituent considered critical in the pharmacophore for mu-opioids. The structural relationship between SC17599 and more traditional opioid ligands was investigated through genetic algorithm-based modeling techniques for pharmacophore generation (GASP) and ligand-receptor docking (GOLD). The relatively planar and electron-rich A ring of the steroid compensated for the lack of aromaticity. Modeling of ligand-receptor docking showed that both morphine and SC17599 occupy the same binding pocket within the transmembrane helix bundle of the mu-opioid receptor and that the relationship between their binding modes largely mimicked the pharmacophore alignment.
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PMID:The steroid 17alpha-acetoxy-6-dimethylaminomethyl-21-fluoro-3-ethoxy-pregna-3, 5-dien-20-one (SC17599) is a selective mu-opioid agonist: implications for the mu-opioid pharmacophore. 1099 35

Glial cell line derived neurotrophic factor (GDNF) signals through a multicomponent receptor complex consisting of RET receptor tyrosine kinase and a member of GDNF family receptor alpha (GFRalpha). Recently, it was shown that tyrosine 1062 in RET represents a binding site for SHC adaptor proteins and is crucial for both RAS/mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3-K)/AKT signaling pathways. In the present study, we characterized how these two pathways diverge from tyrosine 1062, using human neuroblastoma and primitive neuroectodermal tumor cell lines expressing RET at high levels. In response to GDNF stimulation, SHC bound to GAB1 and GRB2 adaptor proteins as well as RET, and SHC and GAB1 were highly phosphorylated on tyrosine. The complex formation consisting of SHC, GAB1 and GRB2 was almost abolished by replacement of tyrosine 1062 in RET with phenylalanine. Tyrosine-phosphorylated GAB1 was also associated with p85 subunit of PI3-K, resulting in PI3-K and AKT activation, whereas SHC-GRB2-SOS complex was responsible for the RAS/ERK signaling pathway. These results suggested that the RAS and PI3-K pathways activated by GDNF bifurcate mainly through SHC bound to tyrosine 1062 in RET. Furthermore, using luciferase reporter-gene assays, we found that the RAS/ERK and PI3-K signaling pathways are important for activation of CREB and NF-kappaB in GDNF-treated cells, respectively. Oncogene (2000) 19, 4469 - 4475.
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PMID:Characterization of intracellular signals via tyrosine 1062 in RET activated by glial cell line-derived neurotrophic factor. 1100 19

Many mammalian retroviruses express their protease and polymerase by ribosomal frameshifting. It was originally proposed that a specialized shifty tRNA promotes the frameshift event. We previously observed that phenylalanine tRNA(Phe) lacking the highly modified wybutoxosine (Y) base on the 3' side of its anticodon stimulated frameshifting, demonstrating that this tRNA is shifty. We now report the shifty tRNA(Phe) contains 1-methylguanosine (m(1)G) in place of Y and that the m(1)G form from rabbit reticulocytes stimulates frameshifting more efficiently than its m(1)G-containing counterpart from mouse neuroblastoma cells. The latter tRNA contains unmodified C and G nucleosides at positions 32 and 34, respectively, while the former tRNA contains the analogous 2'-O-methylated nucleosides at these positions. The data suggest that not only does the loss of a highly modified base from the 3' side of the anticodon render tRNA(Phe) shifty, but the modification status of the entire anticodon loop contributes to the degree of shiftiness. Possible biological consequences of these findings are discussed.
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PMID:1-Methylguanosine in place of Y base at position 37 in phenylalanine tRNA is responsible for its shiftiness in retroviral ribosomal frameshifting. 1114 96

Brain corticotropin-releasing factor (CRF) systems integrate various responses to stress. Pathological responses to stress may result from errors in CRF receptor regulation in response to changes in synaptic CRF levels. To establish an in vitro model to study brain CRF receptors, we characterized the CRF-induced modulation of CRF(1) receptors in the human neuroblastoma cell line, IMR-32. Treatment with CRF decreased CRF(1) receptor binding and desensitized CRF-induced increases in cAMP. The decrease in binding had an EC(50) of approximately 10 nM, was maximal by 30 min, and was blocked by the CRF receptor antagonist [D-Phe(12), Nle(21,38), C(alpha)-MeLeu(37)]CRF(12-41). The desensitization was homologous as vasoactive intestinal polypeptide-induced increases in cAMP were unchanged, and elevation of cAMP did not alter CRF(1) receptor binding. Treatment with CRF for up to 24 h did not alter CRF(1) receptor mRNA levels, suggesting that a posttranscriptional mechanism maintains the decrease in receptor binding. Interestingly, recovery of CRF receptor binding and CRF-stimulated cAMP production was only partial following exposure to 100 nM CRF. In contrast, receptor binding recovered to control levels following exposure to 10 nM CRF. These data suggest that exposure to high doses of CRF result in permanent changes characterized by only partial recovery. Identifying the mechanisms underlying this partial recovery may provide insights into mechanisms underlying the acute and chronic effects of stress on CRF receptor regulation.
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PMID:Persistent corticotropin-releasing factor(1) receptor desensitization and downregulation in the human neuroblastoma cell line IMR-32. 1148 48

The T1P1 strain of Japanese encephalitis (JE) virus was recently isolated from paddy-free Liu-Chiu Islet in which natural JE antibody has been prevalent. In mouse neuroblastoma-derived Neuro-2a cells, T1P1 appeared significantly lower in virus productivity than another local isolate, CH1392. It implied that this new isolate possesses a characteristic viral replication pattern other than that of CH1392. T1P1 has also shown lower neurovirulence, which was reflected by a significantly higher LD(50) (2.44 x 10(6) PFU) than CH1392 (2.87 x 10(2) PFU). In comparison of the full-length RNA sequences between T1P1 and CH1392, a total of 7 nucleotides, including 1 in preM/M and 2 each in NS3, NS5, and the 3'-end noncoding region (NCR), appeared different. Of them, only the changes in NS3 (position 325, T for CH1392, A for T1P1; and position 364, G for CH1392 and A for T1P1) resulted in substitutions of deduced amino acids. There were two additional nucleotide changes appearing in the 3'-NCR. The amino acids 109 Phe and 122 Glu in NS3 of CH1392 were substituted by Ile and Lys, respectively, in T1P1. The unique growth properties and low virulence of T1P1 presented in this report were likely related to abnormal enzymatic activity due to mutations of the NS3 gene (especially position 364) and possibly to the mutations in the 3'-NCR. The natural attenuation of T1P1 that has been circulating in paddy-free Liu-Chiu Islet may account for the absence of clinical JE cases in past years.
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PMID:Mutations in the NS3 gene and 3'-NCR of Japanese encephalitis virus isolated from an unconventional ecosystem and implications for natural attenuation of the virus. 1160 24

The cyclic somatostatin (SST) analogue, cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[BZL]) (cSSTA), has been widely used as somatostatin antagonist. In the human neuroblastoma cell line SH-SY5Y the cyclopeptide acts as a somatostatin receptor agonist. Similar to SST, cSSTA inhibits cell proliferation, activates the protein tyrosine phosphatase SHP-2, and stimulates the activity of mitogen-activated protein kinase. These results suggest that in SH-SY5Y neuroblastoma cells somatostatin receptors may exist which exhibit altered antagonist binding properties.
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PMID:The putative somatostatin antagonist, cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[BZL]), may act as potent antiproliferative agonist. 1218 54

Lectin from a leaf of Erythrina indica was isolated by affinity chromatography on Lactamyl-Seralose 4B. Lectin gave a single band in polyacrylamide gel electrophoresis (PAGE). In SDS-gel electrophoresis under reducing and non-reducing conditions Erythrina indica leaf lectin (EiLL) split into two bands with subunit molecular weights of 30 and 33 kDa, whereas 58 kDa was obtained for the intact lectin by gel filtration on Sephadex G-100. EiLL agglutinated all human RBC types, with a slight preference for the O blood group. Lectin was found to be a glycoprotein with a neutral sugar content of 9.5%. The carbohydrate specificity of lectin was directed towards D-galactose and its derivatives with pronounced preference for lactose. EiLL had pH optima at pH 7.0; above and below this pH lectin lost sugar-binding capability rapidly. Lectin showed broad temperature optima from 25 to 50 degrees C; however, at 55 degrees C EiLL lost more than 90% of its activity and at 60 degrees C it was totally inactivated. The pI of EiLL was found to be 7.6. The amino acid analysis of EiLL indicated that the lectin was rich in acidic as well as hydrophobic amino acids and totally lacked cysteine and methionine. The N-terminal amino acids were Val-Glu-Thr-IIe-Ser-Phe-Ser-Phe-Ser-Glu-Phe-Glu-Ala-Gly-Asn-Asp-X-Leu-Thr-Gln-Glu-Gly-Ala-Ala-Leu-. Chemical modification studies of both EiLL and Erythrina indica seed lectin (EiSL) with phenylglyoxal, DEP and DTNB revealed an absence of arginine, histidine and cysteine, respectively, in or near the ligand-binding site of both lectins. Modification of tyrosine with NAI led to partial inactivation of EiLL and EiSL; however, total inactivation was observed upon NBS-modification of two tryptophan residues in EiSL. Despite the apparent importance of these tryptophan residues for lectin activity they did not seem to have a direct role in binding haptenic sugar as D-galactose did not protect lectin from inactivation by NBS.
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PMID:Purification, some properties of a D-galactose-binding leaf lectin from Erythrina indica and further characterization of seed lectin. 1250 84

In vitro transcription/translation studies with model proteins have shown that glycosylation of Asn-Xaa-Thr sequons is reduced when the sequon is within 60 residues of the C-terminus of the protein. We have previously shown that in living cells N-glycosylation of the prion protein (PrP) is also abolished when its Asn-Ile-Thr and Asn-Phe-Thr sequons are less than 60 residues from the C-terminus (Walmsley and Hooper [2003] Biochemical Journal, 370, 351-355). To investigate whether sequon distance to the C-terminus is a general determinant of N-glycosylation in living cells, Asn-Ile/Phe-Thr sequons were introduced into another glycosylphosphatidylinositol (GPI) anchored protein, membrane dipeptidase (MDP), at similar distances from the C-terminus as those in PrP. When expressed in the human neuroblastoma SH-SY5Y cell line, the introduced sequons were fully N-glycosylated even when they were less than 60 residues from the C-terminus in both GPI-anchored and secreted forms of MDP. These data demonstrate that the utilization of sequons in some proteins is independent of their distance from the C-terminus.
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PMID:Glycosylation efficiency of Asn-Xaa-Thr sequons is independent of distance from the C-terminus in membrane dipeptidase. 1277 76

Peptides which should be generated from the neuropeptide FF (NPFF) precursor were identified in a neuronal (human neuroblastoma SH-SY5Y) cell line and in COS-7 cells after transient transfection of the human proNPFFA cDNA and were compared with those detected in the mouse spinal cord. After reverse-phase high performance liquid chromatography of soluble material, NPFF-related peptides were immunodetected with antisera raised against NPFF and identified by using on-line capillary liquid chromatography/nanospray ion trap tandem mass spectrometry. Neuronal and non-neuronal cells generated different peptides from the same precursor. In addition to NPFF, SQA-NPFF (Ser-Gln-Ala-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-amide) and NPAF were identified in the human neuroblastoma while only NPFF was clearly identified in COS-7 cells. In mouse, in addition to previously detected NPFF and NPSF, SPA-NPFF (Ser-Pro-Ala-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-amide), the homologous peptide of SQA-NPFF, were characterized. These data on intracellular processing of proNeuropeptide FFA are discussed in regard to the known enzymatic processing mechanisms.
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PMID:Identification of proNeuropeptide FFA peptides processed in neuronal and non-neuronal cells and in nervous tissue. 1451 31


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